Department of Orthopedics, Renji Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China.
Mol Med Rep. 2018 May;17(5):6736-6744. doi: 10.3892/mmr.2018.8637. Epub 2018 Feb 27.
Osteosarcoma is one of the most common malignant tumors in adolescent populations and the prognosis remains incompletely understand. Previous reports have demonstrated that microRNA‑124 (miR‑124) has inhibitory effects on various human malignancies and is associated with tumor progression. However, the clinical significance and potential mechanisms of miR‑124 in the progression of osteosarcoma is not clearly understood. In this study, the potential molecular mechanism of miR‑124 in osteosarcoma tumorigenesis, growth and aggressiveness was investigated. The growth, proliferation, apoptosis, migration and invasion of osteosarcoma cells were investigated following miR‑124 transfection were determined by colony formation assay, western blotting, immunofluorescence, migration/invasion assays and reverse transcription‑quantitative polymerase chain reaction. In vivo anti‑cancer effects of miR‑124 were analyzed by a tumor growth assay, immunohistochemistry and survival rate observations. The results demonstrated that miR‑124 transfection significantly decreased integrin expression in osteosarcoma cells, and further inhibited growth, proliferation, migration and invasion of osteosarcoma cells. Flow cytometry assays indicated that miR‑124 transfection attenuated apoptosis resistance of osteosarcoma to tunicamycin, potentially via the downregulation of P53 and Bcl‑2 apoptosis regulator expression. Mechanistic assays demonstrated that miR‑124 transfection suppressed TGF‑β expression in osteosarcoma. An animal study revealed that tumor growth was reduced in tumor cells transfected with miR‑124 compared with control cells, and the survival rate was prolonged in mice with miR‑124 transfected xenografts compared with control tumors. In conclusion, these results indicate that miR‑124 transection inhibits the growth and aggressive of osteosarcoma, potentially via suppression of TGF‑β‑mediated AKT/GSK‑3β/snail family transcriptional repressor 1 (SNAIL‑1) signaling, suggesting miR‑124 may be a potential anti‑cancer agent/target for osteosarcoma therapy.
骨肉瘤是青少年人群中最常见的恶性肿瘤之一，其预后仍不完全清楚。先前的报告表明，微小 RNA-124（miR-124）对各种人类恶性肿瘤具有抑制作用，并与肿瘤进展相关。然而，miR-124 在骨肉瘤进展中的临床意义和潜在机制尚不清楚。在本研究中，研究了 miR-124 在骨肉瘤发生、生长和侵袭中的潜在分子机制。通过集落形成实验、western blot 分析、免疫荧光、迁移/侵袭实验和逆转录-定量聚合酶链反应，检测 miR-124 转染后骨肉瘤细胞的生长、增殖、凋亡、迁移和侵袭情况。通过肿瘤生长实验、免疫组化和生存率观察分析 miR-124 的体内抗癌作用。结果表明，miR-124 转染显著降低骨肉瘤细胞中整合素的表达，并进一步抑制骨肉瘤细胞的生长、增殖、迁移和侵袭。流式细胞术实验表明，miR-124 转染通过下调 P53 和 Bcl-2 凋亡调节因子的表达，减弱骨肉瘤对他莫昔芬的凋亡抵抗。机制研究表明，miR-124 转染抑制骨肉瘤中 TGF-β的表达。动物研究显示，与对照细胞相比，转染 miR-124 的肿瘤细胞的肿瘤生长减少，并且转染 miR-124 的异种移植肿瘤小鼠的生存率延长。总之，这些结果表明，miR-124 转染抑制骨肉瘤的生长和侵袭，可能是通过抑制 TGF-β 介导的 AKT/GSK-3β/snail 家族转录抑制因子 1（Snail-1）信号通路，提示 miR-124 可能是骨肉瘤治疗的一种潜在的抗癌药物/靶点。
